Patients treated for methamphetamine (MA) dependence have a high rate of relapse, and no pharmacotherapy has yet been demonstrated to reduce this rate of relapse. Pharmacotherapy trials for this indication have focused on medications with dopaminergic, serotonergic or mixed mechanisms of action. Although such agents may hold promise, an accumulating body of evidence suggests that adrenergic agents in particular may be efficacious in reducing methamphetamine use. Complementing the core and laboratory components of this grant proposal, we will undertake controlled clinical trials of two adrenergic agents in outpatients who are methamphetamine dependent. Cocaine pharmacotherapy trials have benefited considerably from thoughtful methods of development work leading to, e.g., the Preston criteria for new use , a comparison of outcome measures, and a CPDD-NIDA consensus statement on outcome measures). The field of methamphetamine pharmacotherapy has not had the benefit of the same degree of methods development work. The outpatient component of the center will test the utility of measures of mood, withdrawal, stress, and craving as surrogate markers and test the utility of the quantitative urinalysis measures developed in the laboratory component of this proposal. Specific Aims: 1. To determine the safety of clonidine and carvedilol in the treatment of MA dependence. 2. To determine the effect sizes of clonidine and carvedilol in the treatment of MA. 3. To determine the utility of measures of a) mood, b) methamphetamine withdrawal, c) stress, and d) craving as surrogate markers in methamphetamine dependence. 4. To compare the quantitative urinalysis methods developed in the laboratory component of this proposal to other outcome measures.